RU2764786C1 - Bifunctional insect-rodenticidal agent - Google Patents

Abstract

FIELD: complex deratization and disinsection.

SUBSTANCE: invention relates to a means of complex deratization and disinsection in relation to murine rodents having epidemiological and sanitary significance, as well as their blood-sucking ectoparasites - carriers of causative agents of dangerous infectious diseases, and can be used when carrying out anti-epidemic measures at objects of particular epidemiological significance, in natural foci infectious diseases, as well as in the elimination of the consequences of biogenic emergencies. A bifunctional insecticide-rodenticide agent against murine rodents and ectoparasites includes a rodenticide and an insecticide of a systemic type of action, a grain mixture, a dye, bitrex, a vegetable oil, while as a rodenticide it contains (1-naphthyl) thiourea, and as an insecticide of a systemic type of action it contains fenvalerate and boric acid, with the following ratio of components (wt.%): (1-naphthyl) thiourea - 0.85, fenvalerate - 0.03, boric acid - 0.02, vegetable oil - 5.0, bitrex - 0, 01, dye azorubin - 0.05, grain mixture - the rest.

EFFECT: proposed bifunctional insecto-rodenticidal agent has high rodenticidal and insecticidal efficacy against mice and fleas parasitizing them, does not require special conditions for preparation, has reduced toxicity against non-target species of animals, including humans, birds and fish.

1 cl, 5 tbl, 4 ex

Description

SUBSTANCE: invention relates to medicine and veterinary science, concerns means of complex deratization and disinfestation in relation to mouse-like rodents, as well as their ectoparasites - carriers of pathogens of dangerous infectious diseases. The invention can be used in carrying out anti-epidemic measures at objects of special epidemiological significance, in natural foci of infectious diseases, as well as in eliminating the consequences of biogenic emergencies.

Currently, there are many rodenticides and insecticides, but, basically, they are intended either only for deratization (rodenticides) or only for pest control (insecticides).

Since the carriers of infections are blood-sucking insects - ectoparasites living on the body of rodents, bifunctional agents that exhibit both rodenticide and insecticidal properties are of particular interest. One of the conditions that apply to such means is that arthropod insects (ectoparasites) must die before the host rodent. As a result, the mechanism of transmissible transmission and circulation of the pathogen in the focus is interrupted, which significantly increases the effectiveness of ongoing anti-epidemic measures.

Currently, there are a number of bifunctional agents that have both rodenticide and insecticidal action. Table 1 shows the names of such agents, the active substances included in their composition and the concentrations of these substances [1-9].

All existing bifunctional agents contain anticoagulant substances as rodenticides, and substances with systemic action as insecticides, which cause the death of ectoparasites that parasitize rodents. According to the method of entry into the body of insects, insecticides that cause the death of blood-sucking insects through the blood of animals are classified as systemic insecticides.

Abroad, the effectiveness of drugs that include rodenticide warfarin or difacinone of an anticoagulant type of action and an insecticide from the group of neonicotinoids - imidacloprid of a systemic type of action [10], as well as drugs based on rodenticide bromadiolone and insecticide fipronil [11], has been studied. The efficacy of these agents against rodents and ectoparasites that parasitize them is reported. A large number of baits based on the insecticide fipronil and rodenticides brodifacoum, difetialon, flocumafen, and their mixtures have been patented [12, 13]. Using the example of Rodenticide [13], containing 0.004% fipronil and 0.005% brodifacoum, 100% death of house mice was shown within 5–9 days. The death of cat fleas placed on mice was 100% within 2 days after the first feeding. More than 95% of the added fleas, instead of the dead ones, died within a day after their replanting. This effect continued until the death of the rodent. However, brodifacoum of all existing atcoagulant rodenticides poses the greatest danger due to its extremely high toxicity (LD50 for black and gray rats 0.22 mg/kg, for proteins 0.13 mg/kg). Brodifacoum does not have a pronounced selectivity of action and is dangerous for all mammals, as well as for birds and fish. Brodifacoum has a long excretion time from the body (up to 200 days), is stable in environmental conditions, which, with its large-scale use in natural foci of infectious diseases, can cause serious damage to wildlife [14].

There are no complete data on the effectiveness of existing bifunctional agents in the literature, which complicates the comparative assessment of rodenticide and insecticidal effectiveness. Based on the data on the insecticidal and rodenticidal efficacy of bifunctional agents that were found in the literature, the closest to the claimed agent in terms of availability, purpose, functionality and ability to provide a rodenticidal and insecticidal effect against mouse-like rodents and ectoparasites parasitizing them is the agent "3D- HIT" (LLC "VTV-service, Russia") [4], which was chosen as a prototype tool.

The systemic insecticide acaricide fipronil (0.025 wt. %) from the group of phenylpyrazoles, which has a systemic effect and causes the death of ectoparasites (fleas, rat mites) that parasitize rodents, and rodenticides of the anticoagulant type of action, are included as active substances in the prototype agent "3D-HIT". second generation: flocumafen (0.0025 wt.%) and bromadiolone (0.0025 wt.%). The composition of the product also includes the bitter component bitrex, dyes, flavor, preservative and food fillers. According to the literature [4] means of the prototype has a high rodenticide efficiency. Complete (100%) death of mice occurred on the 5-6th day of observation. Rodenticidal effectiveness of the "ZD-HIT" agent was studied in accordance with the existing regulatory documents that determine the procedure for testing deratization agents [15]. Insecticidal activity was tested according to the method of K. Santora [16]. Hungry rat fleas (X. choopis) after the first, second and third days were planted on mice, which were given the prototype agent "3D-HIT" as food. The death of arthropods was assessed 24 hours after the start of the experiment. On the first day, the death of fleas was 95.9±7.5%; on the second day 75.0±8.7%; by the third 94.7±15.7% [4]. The death of fleas upon contact with poisoned mice was observed only after 24 hours, which allows us to conclude that the insecticidal activity of the prototype agent is not high enough to interrupt the mechanism of transmissible transmission and circulation of the pathogen in the focus of infection.

Another disadvantage of the prototype is associated with the extremely high toxicity of the active substances that make up its composition [3]. Rodenticides bromadiolone and flocumafen, which are part of the prototype, are highly toxic substances and belong to the 1st hazard class according to GOST 12.1.007-76. The insecticide fipronil belongs to the 2nd hazard class. Due to the extremely high toxicity of the active substances that make up the prototype agent, special conditions are required for its preparation: work is carried out in designated rooms with effective supply and exhaust ventilation or in a fume hood, overalls, personal protective equipment, dust respirators are required [3] . The tool cannot be quickly and safely prepared under normal and field conditions.

The objective of the present invention is to create a bifunctional insect-rodenticide agent with high rodenticide and higher insecticidal activity compared to the prototype agent, thanks to which it is possible to carry out effective rodenticide treatment against murine rodents and disinsection against fleas that parasitize rodents, containing active substances lower toxicity, which will make it possible to prepare the claimed agent under normal and field conditions without the use of complex technical means. The creation of such a tool will expand the range of used bifunctional insecticides and rodenticides on the territory of the Russian Federation.

The solution to this problem is achieved by selecting active substances (rodenticide and insecticide) in such a quantitative ratio that after using the bait in the form of a bifunctional agent, rodents die within 6-7 days, while fleas die within 60 minutes after their contact with poisoned mice. . This approach can provide interruption of the mechanism of transmissible transmission and circulation of the pathogen in the focus of infection.

(1-naphthyl)thiourea was chosen as a rodenticide, fenvalerate ((RS)-cyano-3-phenoxybenzyl-(RS)-2-(4-chlorophenyl)-3-methylbutyrate) and boric acid were chosen as insecticides.

To solve this problem, a tool of the following composition is proposed at a ratio of components, wt. %:

(1-naphthyl)thiourea 0.85 fenvalerate 0.03 boric acid 0.02 vegetable oil 5.0 bitrex 0.01 azorubin dye 0.05 grain mixture rest

The listed active substances are not included in any of the existing bifunctional insect-rodenticidal agents. (1-Naphthyl)thiourea belongs to rodenticides of an acute type of action with a rapidly onset toxic effect (within 1-3 days), and is distinguished by a very high selectivity towards murine rodents. The dose of (1-naphthyl)thiourea in the claimed product is selected in such a way as to minimize the toxic effect of the drug on non-target animal and human species, and the rodents die within 6-7 days. In addition, it is known that during deratization measures, the rapid death of rodents scares them away from the bait, and the delayed death of rodents during pest control measures is more effective.

The insecticide fenvalerate is a contact and intestinal insecticide and belongs to the photostable nerve-paralytic pyrethroids. In the claimed agent, fenvalerate is proposed for the first time as a systemic insecticide.

Boric acid belongs to insecticides of contact and intestinal action with a delayed effect. In the claimed product, boric acid is for the first time offered as an auxiliary systemic insecticide. Upon oral intake, boric acid is rapidly and almost completely absorbed from the gastrointestinal tract, enters the bloodstream and is evenly distributed between erythrocytes and plasma [17]. Boric acid disrupts the functions of many systems and organs, in particular the nervous system. Due to this, the nerve-paralytic effect of fenvalerate is enhanced.

The possibility of using fenvalerate and boric acid as systemic insecticides has been identified and confirmed experimentally.

The combined use of fenvalerate and boric acid as systemic insecticides in the proposed agent contributes to the rapid death of fleas, which leads to an interruption of the mechanism of transmissible transmission and circulation of the pathogen in the focus of infectious diseases.

Bitrex (denatonium benzoate) - a substance of an extremely bitter taste that gives a bitter taste to the bait (serves as a "repellent agent"), and the dye azorubine (E122) are introduced into the composition of the product to protect it from being eaten by birds and to prevent accidental poisoning of people and non-target animal species. The dye is also necessary to indicate the distribution of active substances in the claimed product during its preparation.

Vegetable oil is used to ensure the uniformity of the composition during its preparation, as a binder for applying the resulting suspension to the surface of the food base, and also to increase the food attractiveness of the bait for mouse-like rodents.

Unlike the prototype agent, the active components (rodenticide and insecticide) that make up the proposed agent have a lower toxicity [18, 19]. Table 2 shows the names of the active ingredients that make up the claimed agent and the prototype agent, the acute toxicity of active substances (LD50, mg / kg) when administered intragastrically (i.v.) and the hazard class of these substances according to GOST 12.1.007-76.

From the data presented in table 2, it can be seen that the rodenticides bromadiolone and flocumafen, which are part of the prototype product, are extremely dangerous substances and belong to the 1st hazard class according to GOST 12.1.007-76 (LD50 1.125 and 0.46 mg /kg, respectively (rats)). The insecticide fipronil belongs to the 2nd hazard class and is a highly toxic substance (LD50 91-103 mg/kg (rats)). In the claimed product, the most toxic rodenticide is (1-naphthyl)thiourea, which, according to acute toxicity for white rats (LD50 14.4 mg/kg), is classified as hazard class 1 according to GOST 12.1.007-76, and for gray rats ( LD50 25-30 mg/kg) and house mice (LD50 59-60 mg/kg) - to the 2nd hazard class [19]. For other species of mammals, this rodenticide belongs to hazard classes 2 and 3.

The insecticide fenvalerate, which is part of the proposed product, for insects, fish, bees, as well as rats and mice, belongs to the 3rd hazard class, i.e. is a moderately hazardous substance according to GOST 12.1.007-76. Neurotoxic effects and death of mice were observed when they received fenvalerate at a dose of 1000-2000 mg per 1 kg of feed. For humans and other warm-blooded animals, fenvalerate is a low-toxic substance (hazard class 4). For example, no adverse effects of fenvalerate were observed in dogs treated at a dose of 12.5 mg/kg per day for 90 days.

Boric acid, which is part of the proposed product, refers to moderately hazardous substances (hazard class 3 according to GOST 12.1.007-76). However, according to the parameters of acute toxicity when injected into the stomach, applied to the skin and inhaled, insecticides are assigned the 4th hazard class (low-hazard substances).

Thus, according to the toxicity of the active ingredients (Table 2) used in the claimed product in the group "rotenticides" belong to 1-2 hazard classes, while the active ingredients in the prototype product to 1 hazard class, for insecticides - to 3-4 and 2 hazard classes, respectively. Due to the very high toxicity of the active substances that make up the prototype product, the preparation of the product requires a separate room with effective supply and exhaust ventilation and the use of special protective equipment [3]. In view of the fact that the active substances (AD), which are part of the proposed agent, have a lower toxicity than the active substances that are part of the prototype agent, special conditions are not required for the preparation of the claimed agent, overalls (dressing gown, cap, rubber gloves , medical mask) and personal hygiene. The inventive tool can be easily prepared both in stationary and in the field without the use of special technical means.

The claimed agent has a high rodenticidal activity. During 6 days of observation (Table 3), gradual death of rodents takes place and on the 6th day it is more than 90%. In the case of the prototype, the death was 75%.

The inventive agent has a higher insecticidal activity than the prototype agent. During all 6 days of observation (starting from the first), upon contact of fleas with poisoned animals, 100% death of fleas was observed within 60 minutes, while upon contact with rodents poisoned by the prototype agent, 100% death of fleas was not recorded. throughout the entire period of observation (Table 4).

The inventive agent exhibits the property required for bifunctional insect-rodenticidal agents, namely, the death of fleas parasitizing mice occurs before the death of the host rodent.

The claimed agent exhibits a synergistic effect, because observed an increase in both rodenticidal and insecticidal effectiveness of the proposed agent with the combined use of rodenticide (1-naphthyl)thiourea and insecticides fenvalerate and boric acid (Table 5).

The solution of the stated problem is proved by the following examples.

Example 1. Preparation of the claimed agent.

To 5.0 g of vegetable oil add 0.85 g of (1-naphthyl)thiourea, 0.03 g of fenvalerate, 0.02 g of boric acid, 0.01 g of bitrex, 0.05 g of azorubine E122 dye and mix thoroughly. Grain mixture up to 100 g is added to the resulting suspension and mixed thoroughly again.

The inventive tool is easily prepared in stationary and field conditions without the use of complex technical means.

Example 2. Study of the rodenticidal activity of the proposed agent and the prototype agent in relation to mice.

The study of the rodenticidal activity of the proposed agent and the prototype agent was carried out in laboratory conditions in accordance with the current regulatory documents that determine the procedure for testing deratization agents and instructions for their use [15, 20].

For the experiments used non-linear outbred white mice weighing from 18 to 25 g in the amount of 10 individuals in each experiment. The experiments were repeated three times. The food in the form of the claimed agent or the prototype agent was laid out in the feeder in an amount of 20 to 50 g. When eating 2/3 of the feed, a new portion was added to the feeder to the original mass. During the experiment, the animals were provided with free access to water. Observation of the death of animals began the next day after the start of complementary feeding and was observed for 6 days (observation period). Rodenticidal activity was assessed by the number of dead rodents, expressed as a percentage of all those taken in the experiment, as well as by the time of their death. The agent was considered effective if the number of dead mice over 6 days of observation was at least 90% [15].

Statistical processing of the results of the study with the calculation of confidence results was carried out according to generally accepted methods using Student's t-test [21].

The results of experiments to study the rodenticidal efficacy of the proposed agent and the prototype agent in relation to mice are presented in table. 3.

As can be seen from the data in Table. 3, in the case of feeding experimental animals with the prototype agent, the number of dead mice for 6 days of observation was 75%, which indicates the insufficient effectiveness of the prototype agent in relation to mice.

In the case of using the proposed agent, the number of dead mice for 6 days (observation period) reached 90%, which indicates a higher rodenticide effectiveness of the proposed agent.

Example 3. Study of the insecticidal efficacy of the proposed agent and the prototype agent against fleas that parasitize rodents.

To assess the insecticidal effectiveness of the proposed agent and the prototype agent, the replanting method was used [15]. Rat fleas Ceratophyllus fasciitis 1-3 weeks of age (without division by sex) were planted on mice, which were given the claimed agent or the prototype agent as food for 7 days. Observation of insects began the next day after the start of feeding the mice with the claimed agent or the prototype agent and continued for 6 days (observation period). For the experiment, non-linear outbred white mice weighing from 18 to 25 g were used in the amount of 10 individuals in each experiment. Every day, fleas that had not eaten for 1 day were placed on the fur of mice at least 20 individuals per 1 rodent. The experiment was repeated three times. The death of fleas was counted 60 min after replanting. Fleas lying on their backs and unable to roll over on their own were classified as dead. The final count of dead fleas was carried out after 1 day. In control variants, mice and fleas were observed in the same way as in the experiment. Each experience was accompanied by a control, in which fleas were planted on a mouse that received a grain mixture as feed that did not contain the components of the proposed agent or the prototype agent. The death of insects in the control group was not observed during the entire experiment.

Comparative insecticidal effectiveness of the proposed agent and the prototype agent was evaluated by the number of dead fleas (in %). The results of the insecticidal effectiveness of the proposed agent and the prototype agent are presented in table 4.

As can be seen from the data in table 4, the proposed tool has a high insecticidal activity, much higher than when using the prototype. When using the proposed agent, 100% death of fleas was detected on the first and all subsequent days of observation 60 minutes after they were planted on poisoned mice. Arthropods died earlier than host rodents. In the case of the prototype, only on the 3rd day of observation, the death of fleas was 92%, on the next day - 90-96%.

Example 4. Study of the synergistic effect of the proposed agent.

To prove the presence of a synergistic effect in the proposed agent, two formulations were prepared - formulation A and formulation B. Recipe A contained a rodenticide agent (1-naphthyl)thiourea - 0.85 wt. %, vegetable oil - 5 wt. %, bitrex - 0.01 wt. %, dye azorubine - 0.05 wt. %, the rest - grain mixture. Recipe B contained insecticidal agents fenvalerate - 0.03 wt. %, boric acid - 0.02 wt. %, vegetable oil - 5 wt. %, bitrex - 0.01 wt. %, dye azorubine - 0.05 wt. % and the rest - grain mixture. Rodenticide (1-naphthyl)thiourea does not possess insecticidal activity, insecticides fenvalerate and boric acid in such small doses do not cause the death of mice. The rodenticidal efficacy of formulation A and the insecticidal efficacy of formulation B were studied using the methods described in examples 2 and 3. The results of the rodenticidal and insecticidal efficacy of formulations A and B, as well as the proposed agent are presented in table. 5.

Based on the results obtained, presented in table. 5, we can conclude that the claimed agent has a synergistic effect. Rodenticidal efficacy of formula A, which contains only rodenticide (1-naphthyl)thiourea, vegetable oil, bitrex, dye and grain mixture, was low (for 6 days of observation, the death of mice was 40%). When adding fenvalerate and boric acid insecticides (the claimed agent) to formulation A, the death of mice was 90%.

After feeding rodents with formulation B, which contains insecticides fenvalerate and boric acid, vegetable oil, bitrex, dye and grain mixture, the death of fleas parasitizing these rodents reached 100% only on the 3rd day of observation. When the rodenticide (1-naphthyl)thiourea (invented agent) was added to formulation B, the death of fleas was 100% already on the first and subsequent days (the entire observation period). Thus, we observed the mutual potentiation of the active constituents of the substances that make up the proposed agent, to increase both rodenticide and insecticidal activity.

As the results of laboratory studies show, the claimed agent has a high rodenticide and insecticidal efficacy at lower doses of active ingredients. This indicates the achievement of the purpose of the invention and the suitability of the proposed agent for use in anti-epidemic and disinfection measures, namely for simultaneous deratization and disinfestation in natural and anthropogenic foci of zoonotic infections. The use of the proposed agent with a combined insecticidal and rodenticidal action leads to complete death (up to 100%) of arthropod carriers of infectious diseases during the first day of observation, 60 minutes after they are planted on poisoned mice.

Thus, the death of fleas occurs before the death of the host rodent, as a result of which the mechanism of transmissible transmission and circulation of the pathogen in the focus is interrupted, which significantly increases the effectiveness of preventive and extermination measures against mouse-like rodents and arthropods (fleas) parasitizing them.

The claimed tool meets the criterion of "novelty", because For the first time, a highly effective bifunctional agent was proposed, containing as active ingredients a rodenticide (1-naphthyl)thiourea of an acute type of action (0.85 wt.%), leading to a 90% death of mice in the stated dosage within 6 days, and insecticides of nervous paralytic and intestinal-contact type of action - fenvalerate (0.03 wt.%) and boric acid (0.02 wt.%), leading to the complete death of fleas before host rodents. Previously, these components were not used together. An acute type of rodenticide has not previously been used as part of known bifunctional insect-rodenticide agents.

The claimed tool meets the criterion of "inventive step", because From the available sources of information, it is not obvious that (1-naphthyl)thiourea is included in the composition of the proposed agent as a rodenticide and synthetic pyrethroid fenvalerate and boric acid as insecticides. For the first time, according to the method of entry into the body, a systemic effect of insecticides fenvalerate and boric acid was revealed. The fact that the combination of these substances in the optimal quantitative ratio will exhibit a synergistic effect and lead to a significant increase in the rodenticide and insecticidal effectiveness of the proposed agent against mice and fleas that parasitize them is not obvious.

The claimed tool meets the criterion of "suitability for industrial production", tk. the results of the studies performed confirm that the claimed agent has a high level of effectiveness against mouse-like rodents and fleas parasitizing them and can be used in anti-epidemic measures at objects of particular epidemiological significance, in the elimination of foci of dangerous infections, as well as the consequences of biogenic emergencies . The preparation of the proposed agent is simple, and its components are produced by the industry and are freely present on the Russian market. The inventive tool can be prepared both in stationary and in the field without the use of complex technical means. The active components included in the claimed agent have a lower cost than the components included in other bifunctional insecticides and rodenticides.

The claimed agent expands the range of bifunctional insecticides and rodenticides available on the Russian market.

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Claims (2)

A bifunctional insecticide-rodenticide against murine rodents and ectoparasites, including a rodenticide and insecticide of a systemic type of action, a grain mixture, a dye, bitrex, vegetable oil, characterized in that it contains (1-naphthyl)thiourea as a rodenticide, and as a systemic insecticide type of action contains fenvalerate and boric acid, in the following ratio, wt. %: (1-naphthyl)thiourea 0.85 fenvalerate 0.03 boric acid 0.02 vegetable oil 5.0 bitrex 0.01 azorubin dye 0.05 grain mixture rest